Alzheimer's disease is a neurodegenerative disease characterized by progressive loss of memory and cognitive function. It is classifiable as dementia and it is likely to be the fourth most common cause of death in industrialized countries, in addition to causing incalculable social and economic harm. The post-mortem observation of brain tissues of Alzheimer's patients reveals the presence of senile plaques and neurofibrillary tangles in the limbic system and cortex. The plaques, which are mainly present in the extracellular level, contain as a major component the β-amyloid peptide with 40 or 42 amino acids; the β-amyloid peptide (herein abbreviated Aβ) is produced in significant amounts in the brain of patients in the form of monomer, and tends to associate to form increasingly larger aggregates (oligomers, fibrils, plaques). These aggregates are toxic to neurons, leading to their degeneration responsible for progressive loss of cognitive ability and ultimately death. The peptide Aβ, produced in abnormally high amounts in Alzheimer's disease, accumulates in the brain. The dynamic equilibrium between different aggregation forms justifies the fact that the increased production of monomers in the disease, is shifting the equilibrium towards the formation of plaques. The Aβ peptide is also found in the bloodstream where it is possibly in equilibrium, through the blood-brain barrier, with the one present in the brain. As an evidence of the existence of this equilibrium, papers by other authors have shown that the administration of substances capable to bind the peptide Aβ in the blood and to remove it, can to some extent indirectly promote the efflux of Aβ from the CNS: this effects is generally known as “sink effect”.
Whenever successful however, the sink effect has so far obtained a modest, unsatisfactory reduction of the plaque. For example, the literature reports a reduction of the amyloid plaque by using anti-Aβ antibodies or gangliosides; however these substances, beyond providing a modest plaque reduction, are associated with risks of serious side effects on the immune system, e.g. meningoencephalitis (J. Neurosci. 2011, 31(25), 9323-31). The patent application WO 2009/150686 describes liposomes based on cholesterol and sphingomyelin, and a further lipid chosen from cardiolipin, phosphatidic acid and phosphatidylglycerol; these products have a binding capacity with the Aβ peptide in-vitro.
Although some examples of Aβ peptide binding substances are known, at present there is no evidence that any such substances can bring about a therapeutically significant reduction of the amyloid plaque in the brain after systemic administration. The need is therefore felt for treatments being strongly effective against the amyloid plaque in-vivo, so as to represent a valid treatment of Alzheimer's diseases and other neurodegenerative conditions.